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ADULT DATA

TEFLARO®: Proven Effective in
Community-Acquired Bacterial Pneumonia (CABP)

Caused by Susceptible Bacteria

For illustrative purposes only. Not an actual patient.

TEFLARO CABP Study Designs1,4
Type of trial: Two randomized, multicenter, multinational, double-blind, noninferiority trials
Study population: 1231 adults with a diagnosis of CABP
Comparative agents: TEFLARO – 600 mg administered IV over 1 hour every 12 hours for 5-7 days; Ceftriaxone – 1 g ceftriaxone administered IV over 30 minutes every 24 hours for 5-7 days
Adjunctive therapy: CABP Trial 1, two doses on Day 1 of oral clarithromycin 500 mg every 12 hours; CABP Trial 2, no adjunctive macrolide therapy
TEFLARO Study Populations  
Day 4 Population*  
MITT Microbiological Intent-to-treat All subjects with a confirmed bacterial pathogen at baseline.
EmMITT Exploratory Microbiological Modified Intent-to-treat All randomized patients who received any study drug, had CAP that met radiographic criteria and had 1 or more symptoms at baseline, and had 1 or more acceptable baseline typical pathogens.7
Test of Cure (TOC) Populations†  
MITT Modified Intent-to-treat All randomized subjects who received any amount of study drug.
MITTE Modified Intent-to-Treat Efficacy All subjects in the MITT population who were in PORT Risk Class III or IV at baseline.
CE Clinically Evaluable All subjects in the MITTE population who demonstrated sufficient adherence to the protocol. Sufficient adherence is defined as patients who met the minimal disease criteria for CABP and for whom sufficient information regarding the CABP was available to determine the patient's outcome.
ME Microbiologically Evaluable All subjects in the CE population who had at least one typical bacterial pathogen identified at baseline from an appropriate microbiological specimen (eg, blood, sputum, or pleural fluid).
TEFLARO CABP Study Designs1,4
Type of trial:

Two randomized, multicenter, multinational, double-blind, noninferiority trials

Study population:

1231 adults with a diagnosis of CABP

Comparative agents:

TEFLARO – 600 mg administered IV over 1 hour every 12 hours for 5-7 days; Ceftriaxone – 1 g ceftriaxone administered IV over 30 minutes every 24 hours for 5-7 days

Adjunctive therapy:

CABP Trial 1, two doses on Day 1 of oral clarithromycin 500 mg every 12 hours; CABP Trial 2, no adjunctive macrolide therapy

TEFLARO Study Populations Day 4 Population*

MITT Microbiological intent-to-treat

All subjects with a confirmed bacterial pathogen at baseline.

EmMITT Exploratory Microbiological Modified Intent-to-treat

All randomized patients who received any study drug, had CAP that met radiographic criteria and had 1 or more symptoms at baseline, and had 1 or more acceptable baseline typical pathogens.7

Test of Cure (TOC) Populations†

MITT Modified Intent-to-treat

All randomized subjects who received any amount of study drug.

MITTE Modified Intent-to-Treat Efficacy

All subjects in the MITT population who were in PORT Risk Class III or IV at baseline.

CE Clinically Evaluable

All subjects in the MITTE population who demonstrated sufficient adherence to the protocol. Sufficient adherence is defined as patients who met the minimal disease criteria for CABP and for whom sufficient information regarding the CABP was available to determine the patient's outcome.

ME Microbiologically Evaluable

All subjects in the CE population who had at least one typical bacterial pathogen identified at baseline from an appropriate microbiological specimen (eg, blood, sputum, or pleural fluid).

To evaluate the treatment effect of ceftaroline, an analysis was conducted in CABP patients for whom the treatment effect of antibacterials may be supported by historical evidence. This analysis endpoint required subjects to meet sign and symptom criteria at Day 4 therapy: a responder had to both (a) be in stable condition according to consensus treatment guidelines, and (b) show improvement from baseline on at least one symptom of cough, dyspnea, pleuritic chest pain, or sputum production, while not worsening on any of these four symptoms.

The protocol-specified analyses included clinical cure rates at the TOC (8 to 15 days after the end of therapy) in the coprimary MITTE and CE populations and clinical cure rates at TOC by pathogen in the ME population.

TEFLARO CABP studies: Selected patient demographics and baseline characteristics (integrated MITTE)8
Characteristic TEFALRO group
(n=580)
No. (%)
 Ceftriaxone group
(n=573)
No. (%)
Age, median years (range)    
Mean years (±SD) 60.8±16.4 61.6±15.6
>50 years 438 (75.5) 445 (77.7)
≥65 years 273 (47.1) 281 (49.0)
≥75 years 130 (22.4) 128 (22.3)
Sex: male 362 (62.4) 366 (63.9)
Most common comorbid
conditions 		   
Structural lung disease* 160 (27.6) 147 (25.7)
Any prior pneumonia 123 (21.2) 92 (16.1)
Asthma 49 (8.4) 38 (6.6)
PORT risk class of III or IV    
III 360 (62.1) 353 (61.6)
IV 220 (37.9) 220 (38.4)
Bacteremia 23 (4.0) 20 (3.5)
Renal impairment    
Mild (CrCl level, 51-80 mL/min) 199 (34.3) 190 (33.2)
Moderate (CrCl level, 31-50 mL/min) 88 (15.2) 85 (14.8)
WBC count    
<4500 cells /mm3 26 (4.5) 28 (4.9)
4500-10,000 cells/mm3 210 (36.2) 220 (38.4)
>10,000 cells/mm3 229 (39.5) 216 (37.7)
Immature band count    
>10% 9 (1.6) 5 (0.9)
>15% 6 (1.0) 3 (0.5)
TEFLARO CABP studies: Selected patient demographics and baseline characteristics (integrated MITTE)8
TEFLARO group
(n=580)
No. (%) 		Ceftriaxone group
(n=573)
No. (%)
Characteristic
Age, median years (range)
Mean years (±SD)
60.8±16.4 61.6±15.6
>50 years
438 (75.5) 445 (77.7)
≥65 years
273 (47.1) 281 (49.0)
≥75 years
130 (22.4) 128 (22.3)
Sex: male
362 (62.4) 366 (63.9)
Most common comorbid
conditions
Structural lung disease*
160 (27.6) 147 (25.7)
Any prior pneumonia
123 (21.2) 92 (16.1)
Asthma
49 (8.4) 38 (6.6)
PORT risk class of III or IV
III
360 (62.1) 353 (61.6)
IV
220 (37.9) 220 (38.4)
Bacteremia
23 (4.0) 20 (3.5)
Renal impairment
Mild (CrCl level, 51-80 mL/min)
199 (34.3) 190 (33.2)
Moderate (CrCl level, 31-50 mL/min)
88 (15.2) 85 (14.8)
WBC count
<4500 cells /mm3
26 (4.5) 28 (4.9)
4500-10,000 cells/mm3
210 (36.2) 220 (38.4)
>10,000 cells/mm3
229 (39.5) 216 (37.7)
Immature band count
>10%
9 (1.6) 5 (0.9)
>15%
6 (1.0) 3 (0.5)

Data are no. (%) of patients, unless otherwise indicated. CrCl=creatinine clearance; PORT=Pneumonia Outcomes Research Team; WBC=white blood cell.

Defined as any chronic parenchymal or airway disease (eg. chronic obstructive pulmonary disease [emphysema, chronic bronchitis], bronchiectasis, or interstitial fibrosis).

Adapted from File TM et al. Clin Infect Dis. 2010. Reproduced with permission of the Infectious Diseases Society of America.

Next: Clinical Response

CABP Patient Cases See Patient Case

These hypothetical case studies present examples of types of patients who may benefit from TEFLARO.

INDICATIONS AND USAGE

IMPORTANT SAFETY INFORMATION

Contraindications

Warnings and Precautions

Hypersensitivity Reactions

Clostridioides difficile-Associated Diarrhea

Neurological Adverse Reactions

Direct Coombs' Test Seroconversion

Development of Drug-Resistant Bacteria

Adverse Reactions in Adults

Adverse Reactions in Pediatrics

Drug Interactions

Use in Specific Populations

Please also see full Prescribing Information.

References:
  1. TEFLARO® (ceftaroline fosamil) [prescribing information]. Allergan USA, Inc.
  2. Elixhauser A, Owens P. Reasons for being admitted to the hospital through the emergency department, 2003. Healthcare Cost and Utilization Project Statistical Brief #2. February 2006. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb2.pdf. Accessed February 7, 2020.
  3. FDA Guidance ABSSSI. Guidance for industry: acute bacterial skin and skin structure infections: developing drugs for treatment. October 2013. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071185.pdf. Accessed February 7, 2020.
  4. Data on file. Allergan, Inc.
  5. Corey GR, Wilcox M, Talbot GH, et al. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis. 2010;51(6):641-650.
  6. Friedland HD, O'Neal T, Biek D, et al. CANVAS 1 and 2: analysis of clinical response at day 3 in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2015;56(5):2231-2236.
  7. Eckburg PB, Friedland HD, Llorens L, et al. Day 4 clinical response of ceftaroline fosamil versus ceftriaxone for community-acquired bacterial pneumonia. Infect Dis Clin Pract. 2012;20:254-260.
  8. File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, double-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis. 2010;51(12):1395-1405.

TEFLARO® and its design are registered trademarks of Allergan Sales, LLC, an AbbVie company.

© 2023 AbbVie. All rights reserved. US-TEF-230028 06/23

This site is intended for U.S. healthcare professionals only. If you are a patient, and have any questions, please discuss them with your doctor or healthcare professional. For additional information about TEFLARO, call AbbVie Medical Information at 1.800.678.1605.

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IMPORTANT SAFETY INFORMATION

Contraindications

  • TEFLARO is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis has been reported with ceftaroline.

Warnings and Precautions

Hypersensitivity Reactions

  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibacterial drugs. Before therapy with TEFLARO is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Maintain clinical supervision if this product is to be given to a penicillin- or other beta-lactam-allergic patient, because cross sensitivity among beta-lactam antibacterial agents has been clearly established.
  • If an allergic reaction to TEFLARO occurs, discontinue TEFLARO and institute appropriate treatment and supportive measures.

Clostridioides difficile-Associated Diarrhea

  • Clostridioides difficile-Associated Diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including TEFLARO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.

Neurological Adverse Reactions

  • Neurological adverse reactions have been reported during postmarketing surveillance in patients treated with cephalosporins, including TEFLARO. These reactions include encephalopathy and seizures. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after discontinuation of TEFLARO or after hemodialysis. If neurological adverse reactions associated with TEFLARO therapy occur, consider discontinuing TEFLARO or making appropriate dosage adjustments in patients with renal impairment.

Direct Coombs' Test Seroconversion

  • In adults, seroconversion from a negative to a positive direct Coombs’ test result occurred in 120/1114 (10.8%) of patients receiving TEFLARO and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled adult Phase 3 trials.
  • In children, seroconversion from a negative to a positive direct Coombs’ test result occurred in 42/234 (17.9%) of patients receiving TEFLARO and 3/93 (3.2%) of patients receiving comparator drugs in the three pooled pediatric trials.
  • No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with TEFLARO, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of TEFLARO should be considered and supportive care should be administered to the patient if clinically indicated.

Development of Drug-Resistant Bacteria

  • Prescribing TEFLARO in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions in Adults

  • In the four pooled adult Phase 3 clinical trials, serious adverse reactions occurred in 98/1300 (7.5%) of patients receiving TEFLARO and 100/1297 (7.7%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 35/1300 (2.7%) of patients receiving TEFLARO and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse reactions leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the TEFLARO group and 0.5% in the comparator group.
  • The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the adult pooled Phase 3 clinical trials were diarrhea (5%), nausea (4%), and rash (3%).

Adverse Reactions in Pediatrics

  • In the three pooled pediatric clinical trials, serious adverse reactions occurred in 10/257 (4%) of patients receiving TEFLARO and 3/102 (3%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 10/257 (3.9%) of patients receiving TEFLARO and 2/102 (2%) of patients receiving comparator drugs with the most common adverse reaction leading to discontinuation being rash in 2/257 (0.8%) of patients treated with TEFLARO.
  • The most common adverse reactions occurring in ≥ 3% of patients receiving TEFLARO in the pooled pediatric clinical trials were diarrhea (8%), rash (7%), vomiting (5%), pyrexia (3%), and nausea (3%).

Drug Interactions

  • No clinical drug-drug interaction studies have been conducted with TEFLARO. There is minimal potential for drug-drug interactions between TEFLARO and CYP450 substrates, inhibitors, or inducers; drugs known to undergo active renal secretion; and drugs that may alter renal blood flow.

Use in Specific Populations

  • There have been no adequate and well-controlled studies with TEFLARO in pregnant or nursing women. TEFLARO should only be used if the potential benefit justifies the potential risk in these populations.
  • Safety and effectiveness of TEFLARO for the treatment of ABSSSI in pediatric patients less than 34 weeks gestational age and less than 12 days postnatal age have not been established. Safety and effectiveness for the treatment of CABP in pediatric patients below the age of 2 months have not been established as no data are available.
  • Because elderly patients, those ≥65 years of age, are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Dosage adjustment for elderly patients should therefore be based on renal function.
  • Dosage adjustment is required in adult patients with moderate (CrCl >30 to ≤50 mL/min) or severe (CrCl ≥15 to ≤30mL/min) renal impairment and in patients with end-stage renal disease (CrCl <15 mL/min). There is insufficient information to recommend a dosage regimen for pediatric patients with CrCl <50 mL/min/1.73m2.
  • The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established.

Please also see full Prescribing Information.